Single-Agent Ibrutinib Leads to Durable Responses in Relapsed/Refractory MZL

Patients who previously were treated with rituximab saw durable responses when given single-agent ibrutinib, and the drug’s safety profile in a new study matches earlier findings.

A final analysis of phase 2 results shows single-agent ibrutinib is safe and effective as a long-term treatment for patients with relapsed/refractory marginal zone lymphoma (MZL) and that the drug’s efficacy may be related to its ability to disrupt NF-κB signaling. The analysis was published in the journal Blood Advances.

The roughly 7500 people who receive a diagnosis of the B-cell malignancy each year can generally expect to survive for many years. Extranodal MZL has a median overall survival (OS) of 12 years, reported corresponding author Ariela Noy, MD, of Memorial Sloan Kettering Cancer Center, and colleagues. Patients with nodal and splenic MZL have a median OS of 8 years.

Localized MZL can be treated effectively, but advanced disease is incurable. Noy and colleagues said treatment for MZL is typically modeled after that of follicular lymphoma, which has a similar disease course. Yet, key differences in the biology of MZL that suggest it may warrant different treatment.

The phase 2 PCYC-1121 study was developed to help investigators get a better understanding of the safety and efficacy of the Bruton’s kinase inhibitor ibrutinib (Imbruvica) in patients with relapsed/refractory MZL who had previously been treated with rituximab (Rituxan) or rituximab-based chemo-immunotherapy. The trial’s dosage was 560 mg of ibrutinib per day, and 63 patients were enrolled.

This final analysis of the study had a median follow-up of 33.1 months. The overall response rate (ORR) was 58%, with a median duration of response (DOR) of 27.6 months and a median progression-free survival (PFS) was 15.7 months. Median OS was not reached.

“These updated results provide continued evidence of the efficacy and safety of single-agent ibrutinib and support the use of ibrutinib as a chemotherapy-free option for relapsed/refractory MZL,” concluded Noy and colleagues.

Among the 2 patient groups, those who received prior rituximab and those who received rituximab-based chemo-immunotherapy, patients in the former group had better results. They had an ORR of 81% and a median PFS of 30.4 months; median DOR and OS were not reached. Meanwhile, in the chemo-immunotherapy group, the ORR was 51%, DOR was 12.4 months, PFS was 13.8 months, and OS was not reached.

Classified by subtype, patients with extranodal MZL had the highest ORR (63%), followed by patients with splenic MZL (62%) and nodal MZL (47%).

Noy and colleagues said the safety profile of the drug in this study was consistent with earlier reports. Twenty-two percent (n = 14) of patients experienced grade 3 or higher infections, most (n = 10) in the first year. The most common grade 3 or higher treatment-emergent adverse event was anemia, which afflicted 16% of patients.

The authors also undertook an exploratory biomarker analysis, which suggested that NF-κB pathway gene mutations were associated with superior clinical efficacy of ibrutinib. However, they also noted that this finding should be treated with caution given the exploratory nature of the analysis and the small sample size. Future, larger studies would be needed to confirm the finding, they said.


Noy A, de Vos S, Coleman M, et al. Durable ibrutinib responses in relapsed/refractory marginal zone lymphoma: long-term follow-up and biomarker analysis. Blood Adv. 2020;4(22):5773-5784. doi:10.1182/bloodadvances.2020003121